NutriStack
Fluoxetine and MDMA, contraindicated.
MDMA produces its effects by reversing the serotonin transporter; fluoxetine blocks that transporter. The result is unpredictable blunting of MDMA's effect alongside heavy serotonergic load, with documented risk of serotonin syndrome, hyperthermia, and death. Fluoxetine's long half-life (and its active metabolite norfluoxetine) extends this risk for weeks after the last dose.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
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At a glance
- Substances
- Fluoxetine and MDMA
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. MDMA produces its effects by reversing the serotonin transporter; fluoxetine blocks that transporter. The result is unpredictable blunting of MDMA's effect alongside heavy serotonergic load, with documented risk of serotonin syndrome, hyperthermia, and death. Fluoxetine's long half-life (and its active metabolite norfluoxetine) extends this risk for weeks after the last dose.
Mechanism. Fluoxetine occupies SERT, preventing MDMA from triggering reverse transport of 5-HT into the synapse. Despite blunted subjective effects, residual serotonergic activity plus impaired clearance creates conditions for serotonin syndrome and hyperthermia.
Recommendation. Do not combine MDMA with fluoxetine. Because fluoxetine and norfluoxetine persist for 4-6 weeks, do not take MDMA for at least 5 weeks after stopping fluoxetine.
Sources (2)
- Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9. PMID 24006318
- Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Pharmacol Rev. 2003;55(3):463-508. PMID 12869661
Stack Score
How this pair moves the number.
Effect on the composite score
If both Fluoxetine and MDMA are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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